The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates GABAergic transmission as well as migration and morphological maturation of hippocampal neurons

被引：50

作者：

Bassani, Silvia ^{[1
]}

Cwetsch, Andrzej W. ^{[2
]}

Gerosa, Laura ^{[1
]}

Serratto, Giulia M. ^{[1
]}

Folci, Alessandra ^{[1
]}

Hall, Ignacio F. ^{[1
]}

Mazzanti, Michele ^{[3
]}

Cancedda, Laura ^{[2
,4
]}

Passafaro, Maria ^{[1
]}

机构：

[1] CNR, Inst Neurosci, I-20129 Milan, Italy

[2] Ist Italiano Tecnol, Dept Neurosci & Brain Technol, I-16163 Genoa, Italy

[3] Univ Milan, Dept Biosci, I-20133 Milan, Italy

[4] Telethon Dulbecco Inst, Milan, Italy

来源：

HUMAN MOLECULAR GENETICS | 2018年 / 27卷 / 06期

关键词：

GABA(A) RECEPTOR TRAFFICKING; POSTNATAL-DEVELOPMENT; RAT-BRAIN; PROTOCADHERINS; EXPRESSION; MUTATIONS; ENCEPHALOPATHY; INHERITANCE; INHIBITION; DISORDERS;

D O I：

10.1093/hmg/ddy019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABA(A) receptor (GABA(A)R) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABA(A)R surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. In vivo, PCDH19 downregulation impairs migration, orientation and dendritic arborization of CA1 hippocampal neurons and increases rat seizure susceptibility. In sum, these data indicate a role for PCDH19 in GABAergic transmission as well as migration and morphological maturation of neurons.

引用

页码：1027 / 1038

页数：12

共 45 条

[1] The X-Linked Intellectual Disability Protein TSPAN7 Regulates Excitatory Synapse Development and AMPAR Trafficking [J].